TNF inhibitor suppresses bone metastasis in a breast cancer cell line

In the evolution of cancer, tumor necrosis factor-alpha (TNF-alpha) plays a paradoxical role. High doses induce significant anticancer effects, but conversely, physiologic and pathologic levels of TNF-alpha may be involved in cancer promotion, tumor growth, and metastasis. Infliximab is a chimeric murine monoclonal antibody that binds with high affinity to soluble and membrane TNF-alpha and inhibits binding of TNF-alpha to its receptors. In the present study, we investigated the effect of infliximab, a TNF-alpha antagonist, on breast cancer aggressiveness and bone metastases. Infliximab greatly reduced cell motility and bone metastases in a metastatic breast cancer cell line, MDA-MB-231. The mechanism of bone metastasis inhibition involved decreased expression of CXC chemokine receptor 4 (CXCR4) and increased expression of decorin, which is the prototype of an expanding family of small leucine-rich proteoglycans. These results suggest a novel role for TNF-alpha inhibition in the reduction or prevention of bone metastases in this breast cancer model. Our study suggests that inhibition of TNF-alpha using infliximab may become a preventive therapeutic option for breast cancer. (C) 2011 Elsevier Inc. All rights reserved.